Synthesis and evaluation of analogues of the tuberculosis drug bedaquiline containing heterocyclic B-ring units.

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dc.contributor.author Choi, Peter en
dc.contributor.author Sutherland, Hamish en
dc.contributor.author Tong, Amy ST en
dc.contributor.author Blaser, Adrian en
dc.contributor.author Franzblau, Scott G en
dc.contributor.author Cooper, Christopher B en
dc.contributor.author Lotlikar, Manisha U en
dc.contributor.author Upton, Anna M en
dc.contributor.author Guillemont, Jerome en
dc.contributor.author Motte, Magali en
dc.contributor.author Queguiner, Laurence en
dc.contributor.author Andries, Koen en
dc.contributor.author Van den Broeck, Walter en
dc.contributor.author Denny, William en
dc.contributor.author Palmer, Brian en
dc.date.accessioned 2018-11-19T01:41:42Z en
dc.date.issued 2017-12 en
dc.identifier.issn 0960-894X en
dc.identifier.uri http://hdl.handle.net/2292/44451 en
dc.description.abstract Analogues of bedaquiline where the phenyl B-unit was replaced with monocyclic heterocycles of widely differing lipophilicity (thiophenes, furans, pyridines) were synthesised and evaluated. While there was an expected broad positive correlation between lipophilicity and anti-TB activity, the 4-pyridyl derivatives appeared to have an additional contribution to antibacterial potency. The majority of the compounds were (desirably) more polar and had higher rates of clearance than bedaquiline, and showed acceptable oral bioavailability, but there was only limited (and unpredictable) improvement in their hERG liability. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Bioorganic & medicinal chemistry letters en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.subject Microsomes, Liver en
dc.subject Animals en
dc.subject Humans en
dc.subject Rats en
dc.subject Mycobacterium tuberculosis en
dc.subject Heterocyclic Compounds en
dc.subject Antitubercular Agents en
dc.subject Microbial Sensitivity Tests en
dc.subject Administration, Oral en
dc.subject Inhibitory Concentration 50 en
dc.subject Structure-Activity Relationship en
dc.subject Half-Life en
dc.subject Diarylquinolines en
dc.subject ERG1 Potassium Channel en
dc.title Synthesis and evaluation of analogues of the tuberculosis drug bedaquiline containing heterocyclic B-ring units. en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.bmcl.2017.10.042 en
pubs.issue 23 en
pubs.begin-page 5190 en
pubs.volume 27 en
dc.rights.holder Copyright: The author en
dc.identifier.pmid 29107541 en
pubs.end-page 5196 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype brief-report en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype Research Support, U.S. Gov't, Non-P.H.S. en
pubs.subtype Journal Article en
pubs.elements-id 708572 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Auckland Cancer Research en
pubs.org-id Science en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1464-3405 en
pubs.record-created-at-source-date 2017-11-07 en
pubs.dimensions-id 29107541 en


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DOI: 10.1016/j.bmcl.2017.10.042
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